FDA lays path for early Alzheimer’s trials

The Food and Drug Administration’s Center for Drug Evaluation and Research (FDA CDER) has issued a draft guidance to make it easier for development and testing of Alzheimer’s treatments in patients at an early stage of the disease. This may pave the way for researchers to develop trials for patients before they develop overt dementia symptoms.

“Specifically, this guidance addresses the FDA’s current thinking regarding the selection of patients with early AD [Alzheimer’s disease], or patients who are determined to be at risk for developing AD, for enrollment into clinical trials,” the draft guidance states.

“We recognize that the standard approaches to the selection of outcome measures historically used in the development of treatments for dementia of the Alzheimer’s type have major limitations when applied to clinical trials enrolling patients in the early clinical stages of the disease, or before clinical impairment has emerged at all,” the document continues. “This guidance addresses some possible adaptations of the current approach to drug development for the treatment of the dementia stage of AD that appear more appropriate for clinical trials in the early stages of the illness.”

The guidance will help researchers develop trials for very early signs of Alzheimer’s disease, such as Alzheimer’s-precursor prodromal disease. Drug development has become more focused on these early stages, the FDA says, because disease-modifying therapy is thought to be of greater benefit then, though no drugs have yet shown to be effective in that area.

Indeed, development of disease-modifying treatments for early-stage Alzheimer’s have recently fallen short. Johnson & Johnson, along with partners Pfizer and Elan, ended trials of potential disease-altering drug bapineuzumab after clinical trials failed to show any benefit in patients. Eli Lilly’s solanezumab was also determined to be ineffective in patients with more advanced forms of the disease, though it was recently selected for trials in patients at risk for the disease, but not yet presenting symptoms.

“The scientific community and the FDA believe that it is critical to identify and study patients with very early Alzheimer’s disease before there is too much irreversible injury to the brain,” Russell Katz, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “It is in this population that most researchers believe that new drugs have the best chance of providing meaningful benefit to patients.”

For drugs designed to treat patients with overt dementia, the FDA currently requires that treatments not only show an effect on abnormal thinking, but also how well patients function. The goal for these trials is to ensure that any beneficial effect on thinking is associated with a clinically meaningful outcome for the patient. The agency also stated that it is open to considering positive biomarkers as a secondary outcome in combination with a positive primary outcome.

“Guidance for Industry, Alzheimer’s Disease: Developing Drugs for the Treatment of Early Stage Disease” can be found at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM338287.pdf.